This is the second competitive renewal for the Midwest Sexual Transmitted Diseases Cooperative Research Center (STDCRC), a consortium agreement between Indiana University and Northwestern University Schools of Medicine. The primary objective of this Center is to focus the efforts of investigators with different scientific backgrounds and interests on STDs in such a way as to lead to new approaches to primary and secondary prevention. The Midwest STDCRC fosters productive, interdisciplinary, collaboration to enhance the capabilities of individual investigators and to stimulate the entry of other talented investigators into the field. The proposed projects include two focused on genital ulcer disease caused by herpes simplex virus and Haemophilus ducreyl. The first of these will evaluate viral and cellular requirements associated with entry of HSV-1 and HSV-2 into the genital tract using a mouse model of infection, and will also evaluate molecular mechanisms associated with dissemination to the nervous system. The second will utilize a human challenge model of infection to evaluate the role of the cutaneous immune response to H. ducreyl in pathogenesis. Two projects focus on different aspects of human papillomavirus (HPV) infections. One investigates mechanisms by which the E7 gene product of high risk HPV contributes to the development of anogenital malignancies. The second seeks to define the extent to which immunosuppression associated with transplantation of pregnancy results in reaction and expression of latent HPV infection; while a third project is focused on the mechanisms by which gene expression and replication of HPV are regulated by silencer and other genetic elements. Consistent with the objective primary prevention is a project which seeks to define the timing of recurrent sexually transmitted infections and their relationship to inter- and intra- personal factors which may modify the risk of recurrent infection. These projects will be supported by a Biostatistical Core, and a Clinical/Laboratory Core with the latter monitoring sexually transmitted diseases as biological markers for evidence of recurrent infection. This core will also collect specimens and data from individuals infected with different sexually transmitted pathogens and distribute them, along with appropriate clinical data, to the various projects. The extensive collaborations and cross-disciplinary fertilization which exists among the different projects will be reinforced by frequent scientific/administrative meetings to assess progress of each projects and provide constructive criticism and assistance.